Abstract-Upregulation of endothelial adhesion molecules is the earliest step of atherogenesis. Whether obesity induces endothelial adhesin upregulation is unknown. To address this topic, circulating vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and von Willebrand factor (vWF) Obesity and central body fat disposition have been correlated with a higher prevalence of cardiovascular death in low-risk subjects. 4 The relative risk of cardiovascular death associated with an increment of 1 kg/m 2 in body mass index (BMI) is 1.10 and 1.08 for adult men and women, respectively. 1 Thus, although the influence of other risk factors such as low physical activity and excess alcohol intake 2 cannot be excluded, obesity acts as an independent cardiovascular risk factor.Upregulation of endothelial adhesins of the selectin family 5 (E-selectin and P-selectin) and of the immunoglobulin superfamily 6 [intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)] allows the attachment of circulating cells to the endothelium and represents the initiating event in atherogenesis. 7,8 Upregulation of adhesin genes leads to the expression of membraneassociated adhesins and release of their soluble forms. Thus, circulating soluble adhesin levels act as markers of in vivo adhesin expression. 8 -11 Accordingly, plasma soluble E-selectin concentrations were found to be elevated in conditions associated with increased risk for developing atherosclerosis, ie, type 2 diabetes 12,13 and hypertension. 14 Similarly, plasma soluble VCAM-1, ICAM-1, and E-selectin concentrations were found to be elevated in glucoseintolerant hypertensives. 15 Augmented levels of circulating von Willebrand factor (vWF), a marker of in vivo endothelial damage, 16 were found in nonatherosclerotic obese persons. 17 Furthermore, circulating levels of endothelin-1 18 and tissue plasminogen activator-1 19 were increased while endotheliumdependent vasodilation 20 was reduced in normotensive obese individuals.Taken together, the above data support the concept that obesity per se might induce early endothelial activation in humans. In view of the possible relationship between such endothelial activation and obesity, we evaluated circulating

The present study shows that iron can directly interact with human platelets, resulting in their activation. Its action is mediated by OH. formation and involves PKC activity. Our findings provide an additional contribution to the understanding of the mechanism(s) by which iron overload might promote atherosclerosis and coronary artery disease.

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